774 



NA TURE 



[December 9, 1922 



The Use of a Pancreatic Extract in Diabetes. 1 



By Sir C. S. Sherrin 



IN the words of its charter, repeated at the admis- 

 sion of each new fellow, the Royal Society is 

 described as instituted " for Improving Natural Know- 

 ledge." A main means for that "improving" is dis- 

 covery. In the case of natural knowledge the main 

 road to discovery must lie in research. There are 

 several ways in which research can be encouraged, 

 and one of them lies in providing suitable workers 

 with the means to devote their time freely to investi- 

 gation. The society is fortunate in possessing now, to 

 a somewhat greater extent than formerly, funds that 

 may be considered as permanently allocated to this 

 fundamental object ; for though its existence extends 

 now to more than two and a half centuries, financial 

 help directed to this eminently important aim has 

 come only relatively recently. That it should have 

 now begun may be a sign of the arrival of an Age in 

 some respects new ; the beginning of a trend towards 

 wider public interest in and sympathy with research. 



Of events in biological science in the past year 

 I may mention one that is attracting attention 

 at this time. In the Physiological Laboratory of 

 Toronto University has been prepared a pancreatic 

 extract possessing striking power over the carbohydrate 

 metabolism of the body. Potent as it is, experience 

 with it is still limited. Work of urgency is required 

 with what may prove to be a desired remedy ; the 

 first programme is further investigation of the extract's 

 full properties, with caution as to raising hopes which 

 practice mav but partly fulfil. Such are the considera- 

 tions which weigh with the Canadian — and the discovery 

 is from a Canadian university — to whom the discovery is 

 due. In this country the Medical Research Council has 

 undertaken public-spirited direction of the extract's pre- 

 paration and of further determination of its properties. 



The physiological steps of the discovery may be 

 briefly outlined thus : — Destruction of the pancreas 

 is well known to produce in the dog a diabetes-like 

 condition, rapidly fatal. The liver's store of glycogen 

 is lost, and cannot be renewed by even liberal supply 

 of its normal source, carbohydrate food. Sugar 

 formation from proteins ensues, with rapid wasting 

 of the tissues ; at the same time the blood is sur- 

 charged with sugar, and the tissues are unable to make 

 use of sugar. In a normal animal, glucose put into 

 the circulation raises the ratio of carbon dioxide expired 

 to oxygen absorbed, because the tissues consume the 

 sugar. But glucose similarly introduced into the de- 

 pancreated diabeticanimal does not raise the respiratory 

 quotient; the tissues no longer consume the sugar. The 

 inference has long been that the pancreas produces some 

 substance enabling the body to make use of sugar — some 

 substance that in fact should control certain forms of ' 

 diabetes. At Toronto there seems to have been secured 

 the extraction of that substance. 



The pancreas consists of two structures intimately 

 commingled. One, secreting cells set round ducts 

 into which they pour the pancreatic juice, is potently 

 ■ 1 1 [i stive : the other, scattered in tiny islets, is seemingly 

 unrelated to the ducts though closely related to the 

 blood channels. The want of success of pancreatic 

 extracts in mitigating a diabetic condition might be 



NO. 2771, VOL. I to] 



gton, G.B.E., P.R.S. 



due to digestive powers of the juice cells destroying 

 an anti-diabetic substance of the islet-cells. Dr. F. G. 

 Banting determined to avoid this possibility by 

 preparing extracts made from the pancreas after its 

 trypsin-yielding cells had been selectively brought to 

 atrophy by ligation of the gland ducts. He and Mr. 

 Best, a collaborator who joined him, overcoming 

 formidable difficulties of technique, succeeded in 

 preparing the required material, and in examining 

 the effect of extract upon diabetic depancreated dogs. 

 They found the sugar fall both in the blood and urine, 

 and that the animals, instead of dying in three weeks, 

 remained, while treated, in excellent condition. 



The further prosecution of the work afterwards 

 engaged other collaborators : to mention them in 

 alphabetical order , Collip, Hepburn, Latchford, MacLeod, 

 and Noble ; of these Prof. MacLeod, himself director 

 of the Toronto Physiological Laboratory, is well known 

 as a skilled authority in experiments on carbohydrate 

 metabolism, and Dr. Collip is professor of bio-chemistry 

 in the University of Alberta, though ' temporarily 

 working at Toronto. With team work, advance has 

 proceeded relatively quickly, and successful extracts 

 are now obtained from ordinary ox and other pancreas. 



Of much physiological interest is the fact that the 

 active principle in the extract seems one normally 

 controlling the blood-sugar in health, for its injection 

 rapidly lessens the blood-sugar in normal animals. 

 The extract, added to a simple perfusion fluid containing 

 a little glucose and streamed through the isolated rabbit 

 heart, increases three- or fourfold the heart's uptake of 

 sugar from the fluid. The extract sometimes evokes ' 

 serious nervous disturbances seemingly associated with 

 extreme fall in the amount of the blood-sugar. 



Administered to diabetic depancreated animals, the 

 extract brings reappearance of the liver's glycogen 

 store, while bringing down the sugar excess in the blood 

 and the excretion of sugar and acetone in the urine ; 

 and it enables the diabetic organism to consume 

 sugar. It also lessens or prevents hyperglycemia 

 produced in animals in several other wavs. 



Gratifying success has already attended the use of 

 this extract in the relief of diabetic patients ; much 

 further research is, however, yet needed for develop- 

 ment of the methods of extraction and of the routine 

 use of the active principle. 



The important physiological advance thus just 

 reached comes as a fit reward to those who have 

 ai hieved it. It is, of course, the striking result 

 of steady work pursued by many various workers 

 through many earlier years. Such work, we may 

 remember, lay often open to charge by the unenlightened 

 of being merely academic and fruitless, its reward 

 being at the time simply the intrinsic scientific interest 

 of the facts obtained. The Toronto investigators we may 

 be sure would say with Pasteur, " To have the fruit there 

 must have been cultivation of the tree." Part of the 

 merit of the recent successful investigation has been 

 its appreciation of possibilities indicated by previous 

 work. But that merit is after all only a preliminary to 

 the main achievement. The actual achievement is 

 the deserved success of a bold attack conducted with 

 conviction and determination and carried through in 

 the face of formidable experimental difficulties. 



